Animal Models for Postoperative Implant-Related Spinal Infection.

Postoperative infections following implant-related spinal surgery are severe and disastrous complications for both orthopaedic surgeons and patients worldwide. They can cause neurological damage, disability, and death. To better understand the mechanism of these destructive complications and intervene in the process, further research is needed. Therefore, there is an urgent need for efficient, accurate, and easily available animal models to study the pathogenesis of spinal infections and develop new and effective anti-bacterial methods. In this paper, we provide a general review of the commonly used animal models of postoperative implant-related spinal infections, describe their advantages and disadvantages, and highlight the significance of correctly choosing the model according to the infection aspect under investigation. These models are valuable tools contributing to the better understanding of postoperative spinal infections and will continue to facilitate the invention of novel preventative and treatment strategies for patients with postoperative spinal infections. However, although they are valid and reproducible in some respects, the current animal models present certain limitations. Future ideal spinal infection animal models may assess the bacterial load of the same animal in real-time in vivo, and better mimic the human anatomy as well as surgical techniques. Strains other than Staphylococcus aureus account for a large proportion of postoperative spinal infections, and thus, the establishment of models to evaluate other types of microbial infections is expected in the future. Furthermore, novel transgenic models established on advancements in genome editing are also likely to be developed in the future.

Effect of Whitlockite as a new bone substitute for bone formation in spinal fusion and ectopic ossification animal model.

BACKGROUND: Bone substrates like hydroxyapatite and tricalcium phosphate have been widely used for promoting spinal fusion and reducing the complications caused by autograft. Whitlockite has been reported to promote better bone formation in rat calvaria models compare with them, but no study investigated its effect on spinal fusion yet. Also, the higher osteoinductivity of whitlockite raised concern of ectopic ossification, which was a complication of spinal fusion surgery that should be avoided. METHODS: In this study, we compared the osteoinductivity of whitlockite, hydroxyapatite, and tricalcium phosphate porous particles with SD rat spine posterolateral fusion model and investigated whether whitlockite could induce ectopic ossification with SD rat abdominal pouch model. RESULTS: The micro-CT result from the posterolateral fusion model showed whitlockite had slightly but significantly higher percent bone volume than tricalcium phosphate, though none of the materials formed successful fusion with surrounding bone tissue. The histology results showed the bone formed on the cortical surface of the transverse process but did not form a bridge between the processes. The result from the abdominal pouch model showed whitlockite did not induce ectopic bone formation. CONCLUSION: Whitlockite had a potential of being a better bone substrate hydroxyapatite and tricalcium phosphate in spinal fusion with low risk of inducing ectopic ossification.

Comparison of demineralized bone matrix and hydroxyapatite as carriers of Escherichia coli recombinant human BMP-2.

BACKGROUND: Autograft has been widely used in various orthopedic and dental surgery for its superior osteogenicity, osteoinductivity and osteoconductivity. But the available volume of the autograft is limited and the efficacy of it is highly affected by the condition of the patients. Therefore, growth factors such as Escherichia coli bone morphogenetic protein-2 (ErhBMP-2) has been widely used in some countries and regions with various carriers that could affect the effects of the growth factors. Demineralized bone matrix (DBM) has been widely used as a bone graft substitute and growth factor carrier, but its effect as a carrier of ErhBMP-2 was less investigated. MATERIALS AND METHODS: Rat calvaria defect model was used in this study. We implanted ErhBMP-2 with DBM or hydroxyapatite (HA) as a carrier in 8 mm calvaria defect and compared their bone regeneration effect in 4th week and 8th week after implantation with micro-CT and histology. The data was analyzed with one-way ANOVA method with Bonferroni post-hoc analysis. RESULT: The group with DBM as the carrier showed significantly higher bone volume and bone thickness than the groups with HA as the carrier in both weeks. And the histology sections showed less adipose tissue formed in the groups with DBM as the carrier. CONCLUSION: DBM could be a better carrier for ErhBMP-2 than HA.

Postoperative discal pseudocyst and its similarities to discal cyst: A case report.

BACKGROUND: Postoperative discal pseudocyst (PDP) is a rare condition that presents after surgery for lumbar disc herniation. Due to the lack of information, the diagnosis and treatment of PDP remain controversial. Herein, we report a PDP case that occurred following percutaneous endoscopic lumbar discectomy and received conservative treatment. Additionally, we review all the published literature regarding PDP and propose our hypothesis regarding PDP pathology. CASE SUMMARY: A 23-year-old man presented with a relapse of low back pain and numbness in his left lower extremity after undergoing percutaneous endoscopic lumbar discectomy for lumbar disc herniation. Repeat magnetic resonance imaging demonstrated a cystic lesion at the surgical site with communication with the inner disc. The patient was diagnosed as having PDP. The patient received conservative treatment, which resulted in rapid improvement and spontaneous regression of the lesion, and had a favorable outcome in follow-up. CONCLUSION: PDP and discal cyst (DC) exhibit similarities in both histological and epidemiological characteristics, which indicates the same pathological origin of PDP and DC. The iatrogenic annular injury during discectomy might accelerate the pathological progression of DC. For patients with mild to moderate symptoms, conservative treatment can lead to great improvement, even inducing spontaneous regression. However, surgical cystectomy is necessary in patients with neurological deficits and where conservative treatment is ineffective.

A novel 3D indirect co-culture system based on a collagen hydrogel scaffold for enhancing the osteogenesis of stem cells.

In this study, the paracrine effect between adipose-derived mesenchymal stem cells (ADSCs) and osteoblasts was investigated in collagen-based three-dimensional (3D) scaffolds. 3D encapsulation of mesenchymal stem cells in hydrogel scaffolds was conducted for bone tissue regeneration. Osteoblasts were encapsulated in alginate microbeads with uniform size, which could be controlled by varying the supply voltage using electrostatic droplet extrusion. Osteoblast-encapsulated microbeads were embedded with ADSCs in collagen bulk hydrogel scaffolds with a high survival rate. The separated space between the two types of cells made it possible to confirm ADSC differentiation into osteogenic lineages in the 3D collagen hydrogel scaffold by the paracrine effect in vitro. Furthermore, co-cultured ADSC and osteoblasts showed enhanced bone formation compared with the ADSC monoculture group in the rat calvarial defect model. The system developed in this study provides a novel in vitro tissue model for bone regeneration without exogenous factors, and it has the potential to be used to study the paracrine effect in various co-culture systems in the near future.

BMP-2 and hMSC dual delivery onto 3D printed PLA-Biogel scaffold for critical-size bone defect regeneration in rabbit tibia.

3D printing technology has various advantages, and the incorporation of bioactive substances into the 3D printed scaffold provides the biological and architectural characteristics of the scaffolds, which is very important for obtaining a good osseointegration effect. In this relation, this study prepared a novel porous hollow cage poly(lactic acid) (PLA) 3D printed scaffold and combined recombinant human bone morphogenetic protein-2 (rhBMP-2) and/or mesenchymal stem cells (MSCs) with Biogel composed of gelatin and alginate. Then, the scaffolds were used to evaluate the resulting bone regeneration through both in vitro and in vivo tests. The experimental group was divided into four groups as follows: only PLA scaffold (PLA); PLA scaffold filled with BMP-2 loaded on Biogel (P-BG-B2); PLA scaffold filled with MSCs encapsulated Biogel (P-BG-M); PLA scaffold filled with both BMP-2 and MSCs loaded on Biogel (P-BG-B2-M). Then in vitro results showed that the PLA-Biogel-based scaffold increased cell proliferation, and the P-BG-B2-M group showed a higher alkaline phosphatase activity and bone-related gene expression than was seen with the P-BG-M group at all the time points. It was shown that four weeks post-operative micro-CT analysis showed that within the defect site the P-BG-B2 group had a significantly higher percent bone volume (BV/TV) than the PLA group and P-BG-M group. And, out of the defect site, the P-BG-B2-M group BV/TV was shown significantly higher than the PLA group (p < 0.05). Histologically, defects in the P-BG-B2-M group showed a homogeneous new bone distribution, however the P-BG-B2 group and P-BG-M group presented a notably higher bone formation in the internal region than in the proximal region of the bone defect site. In conclusion, the 3D PLA-Biogel-based scaffold adapted rhBMP-2 and MSCs with carrier PLA showed good biocompatibility and high possibility as an effective and satisfactory bone graft material.

Relationship between Long Noncoding RNA H19 Polymorphisms and Risk of Coronary Artery Disease in a Chinese Population: A Case-Control Study.

METHODS: We collected 732 samples from Liaoning Province, China, and three polymorphisms in long noncoding RNA H19 were genotyped using the KASP platform. RESULTS: Our data showed that H19 rs2735971 and rs3024270 variant genotypes were associated with a decreased risk of CAD (rs2735971, P = 0.003, odds ratio (OR) = 0.6195, 95% confidence interval = 0.44 - 0.84; rs3024270, P = 0.030, OR = 0.65, 95% confidence interval = 0.44 - 0.96). No significant association with the risk of CAD was found for H19 rs2839698 polymorphism (P > 0.05). In haplotype analysis, H19 polymorphisms of rs2735971-rs2839698-rs3024270 A-C-C haplotype reduced the risk of CAD by 0.61-fold (P = 0.004, OR = 0.61, 95% confidence interval = 0.43-0.86). In addition, we found that rs2839698 interacted with smoking (P interaction = 0.027), and according to multifactor dimensionality reduction analysis, the three-factor model including H19 rs2839698-smoking-drinking was the best model for the risk of CAD (testing balanced accuracy = 0.6979). CONCLUSION: Our study demonstrated that some genotypes of H19 rs2735971 and rs3024270 polymorphisms, as well as rs2735971-rs2839698-rs3024270 A-C-C haplotype, were associated with the risk of CAD in a Chinese population, and these genotypes have the potential to be biomarkers for predicting CAD risk. We also found that rs2735971-rs2839698-rs3024270 A-C-C may have a significantly lower risk of CAD. The recessive genetic model of rs3024270 could predict the severity of CAD.

Noncoding RNAs as Biomarkers for Acute Coronary Syndrome.

Acute coronary syndrome (ACS), consisting of acute myocardial infarction and unstable angina, is the most dangerous and fatal form of coronary heart disease. Acute coronary syndrome has sudden onset and rapid development, which may lead to malignant life-threatening conditions at any time. Therefore, early detection and diagnosis are critical for patients with ACS. Recent studies have found that noncoding RNA is of great significance in the diagnosis and treatment of cardiovascular diseases. In this review, we summarized recent data on circulating noncoding RNAs (including microRNA, long noncoding RNA, and circular RNA) as diagnostic and prognostic markers in ACS including acute myocardial infarction and unstable angina. Specifically, microRNAs (miRNAs) as diagnostic markers are divided into three types: miRNAs of increased expression in ACS, miRNAs of decreased expression in ACS, and miRNAs of contradictory expression in ACS. Moreover, we described these miRNAs of increased expression in ACS based on miRNAs family. This review may result in a great guidance of noncoding RNAs as biomarkers for ACS in clinical practice.

Effect of medications on prevention of secondary osteoporotic vertebral compression fracture, non-vertebral fracture, and discontinuation due to adverse events: a meta-analysis of randomized controlled trials.

BACKGROUND: Bone loss with aging and menopause increases the risk of fragile vertebral fracture, osteoporotic vertebral compression fracture (OVCF). The fracture causes severe pain, impedes respiratory function, lower the quality of life, and increases the risk of new fractures and deaths. Various medications have been prescribed to prevent a secondary fracture, but few study summarized their effects. Therefore, we investigated their effects on preventing subsequent OVCF via meta-analyses of randomized controlled trials. METHODS: Electronic databases, including MEDLINE, EMBASE, CENTRAL, and Web of Science were searched for published randomized controlled trials from June 2015 to June 2019. The trials that recruited participants with at least one OVCF were included. We assessed the risk of bias of every study, estimated relative risk ratio of secondary OVCF, non-vertebral fracture, gastrointestinal complaints and discontinuation due to adverse events. Finally, we evaluated the quality of evidence. RESULTS: Forty-one articles were included. Moderate to high quality evidence proved the effectiveness of zoledronate (Relative Risk, RR: 0.34; 95% CI, 0.17-0.69, p = 0.003), alendronate (RR: 0.54; 95% CI: 0.43-0.68; p < 0.0001), risedronate (RR: 0.61; 95% CI: 0.51-0.73; p < 0.0001), etidronate (RR, 0.50; 95% CI, 0.29-0.87, p < 0.01), ibandronate (RR: 0.52; 95% CI: 0.38-0.71; p < 0.0001), parathyroid hormone (RR: 0.31; 95% CI: 0.23-0.41; p < 0.0001), denosumab (RR, 0.41; 95% CI, 0.29-0.57; p < 0.0001) and selective estrogen receptor modulators (Raloxifene, RR: 0.58; 95% CI: 0.44-0.76; p < 0.0001; Bazedoxifene, RR: 0.66; 95% CI: 0.53-0.82; p = 0.0002) in preventing secondary fractures. Moderate quality evidence proved romosozumab had better effect than alendronate (Romosozumab vs. alendronate, RR: 0.64; 95% CI: 0.49-0.84; p = 0.001) and high quality evidence proved that teriparatide had better effect than risedronate (risedronate vs. teriparatide, RR: 1.98; 95% CI: 1.44-2.70; p < 0.0001). CONCLUSION: Zoledronate, alendronate, risedronate, etidronate, ibandronate, parathyroid hormone, denosumab and selective estrogen receptor modulators had significant secondary prevention effects on OVCF. Moderate quality evidence proved romosozumab had better effect than alendronate. High quality evidence proved PTH had better effect than risedronate, but with higher risk of adverse events.

LncRNA MALAT1 gene polymorphisms in coronary artery disease: a case-control study in a Chinese population.

Background: Coronary artery disease (CAD) is one of the main fatal diseases all over the world. CAD is a complex disease, which has multiple risk factors mechanisms. In recent years, genome-wide association study (GWAS) had revealed single nucleotide polymorphism genes (SNPs) which were closely related with CAD risks. The relationship between long non-coding RNA (lncRNA) MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) and CAD risk is largely unknown. To our knowledge, this is the first study which demonstrated the interaction effects of SNP-SNP and SNP-environment with CAD risk. In general, our case-control study is to detect the association between MALAT1 (rs619586, rs4102217) SNPs and CAD risk. Methods: Three hundred and sixty-five CAD patients and three hundred and eighty-four matched control participants blood samples were collected in Liaoning province, China. Two polymorphisms (rs619586, rs4102217) in lncRNA MALAT1 were genotyped by KASP platform. Results: In a stratified analysis, we found that non-drinkers with GC genotype and the recessive model of rs4102217 had higher CAD risk (P=0.010, odds ratio (OR): 1.96, 95% confidence interval (CI) = 1.17-3.28; P=0.026, OR: 1.73, 95% CI = 1.07-2.79) and diabetes mellitus (DM) history group (P=0.010, OR: 4.07, 95% CI = 1.41-11.81; P=0.019, OR: 3.29, 95% CI = 1.22-8.88). In SNP-SNP interactions analysis between MALAT1 and CAD risk, we found rs4102217 had an increase in smokers (GG: OR: 2.04, 95% CI = 1.42-2.92; CC+GC: OR: 2.64, 95% CI = 1.64-4.26) and a decrease in drinkers (CC+GC: OR: 0.33, 95% CI = 0.20-0.55). Smokers with MALAT1 rs619586 AA genotype (OR: 2.20, 95% CI = 1.57-3.07) and GG+AG genotype (OR: 2.11, 95% CI = 1.17-3.81) had a higher risk of CAD. Moreover, drinkers with AA genotype (OR: 0.22, 95% CI = 0.10-0.48) and GG+AG genotype (OR: 0.38, 95% CI = 0.22-0.65) had a lower risk of CAD. According to the MDR software, MALAT1 rs4102217 polymorphism-smoking-drinking was the best interaction model, which has higher risk of CAD (Testing Bal.ACC. = 0.6979). Conclusion: Our study demonstrated that the GC genotype and the recessive model of rs4102217 potentially increased CAD risk in some specific group.

Mesenchymal Stem Cell Therapy for Bone Regeneration.

Mesenchymal stem cells (MSCs) have been used in clinic for approximately 20 years. During this period, various new populations of MSCs have been found or manipulated. However, their characters and relative strength for bone regeneration have not been well known. For a comprehensive understanding of MSCs, we reviewed the literature on the multipotent cells ranging from the definition to the current research progress for bone regeneration. Based on our literature review, bone marrow MSCs have been most widely studied and utilized in clinical settings. Among other populations of MSCs, adipose-derived MSCs and perivascular MSCs might be potential candidates for bone regeneration, whose efficacy and safety still require further investigation.

Associations between circulating IgG antibodies to Apolipoprotein B100-derived peptide antigens and acute coronary syndrome in a Chinese Han population.

Objectives: Acute coronary syndrome (ACS) is the major cause of mortality worldwide and caused mainly by atherosclerosis of coronary arteries. Apolipoprotein B100 (ApoB100) is a major component of low-density lipoprotein (LDL) and its oxidation can trigger inflammation in vascular endothelial cells leading to atherosclerosis. The association between antibodies to ApoB100-derived antigens and atherosclerotic diseases has been studied in recent years, but the findings appear to be controversial. The present study developed an ELISA in-house with ApoB100-derived peptide antigens to circulating anti-ApoB100 IgG antibodies in patients with ACS. Methods: Fifteen ApoB100-derived peptide antigens (Ag1-Ag15) were designed to develop an in-house ELISA for the detection of circulating anti-ApoB100 IgG levels in 350 patients with ACS and 201 control subjects amongst a Chinese population. Binary logistic regression was applied to examine the differences in anti-ApoB IgG levels between the patient group and the control group with adjustment for a number of confounding factors; the correlation between anti-ApoB100 IgG levels and clinical characteristics was also tested. Results: Patients with ACS had significantly higher levels of plasma IgG for Ag1 (adjusted P<0.001) and Ag10 antigens (adjusted P<0.001). There was no significant increase in the levels of IgG to the other 13 antigens in these ACS patients. In the control group, anti-Ag10 IgG levels were positively correlated with age, high-density lipoprotein (HDL), and ApoA levels (P≤0.001 for all) and negatively correlated with blood triglyceride (TG) (P=0.008); in the patient group, anti-Ag10 IgG levels were positively correlated with LDL (P=0.003), and negatively correlated with ApoA (P=0.048) and systolic blood pressure (SBP) (P=0.036). The area under ROC (receiver operator characteristic) curve (AUC) was 0.612 (95% confidence interval (CI): 0.560-0.664; P<0.001) in anti-Ag1 IgG assay and 0.621 (95% CI: 0.569-0.672; P<0.001) in anti-Ag10 IgG assay. Conclusion: Circulating IgG for ApoB100-derived peptide antigens may be a useful biomarker of ACS, although anti-ApoB IgG levels were not associated with the coronary artery plaque burden characterized by the coronary Gensini score.

Hemodynamic and gas exchange effects of inhaled iloprost in patients with COPD and pulmonary hypertension.

Studies have shown that vasodilators such as iloprost can be useful for treating pulmonary hypertension (PH). However, in patients with COPD, vasodilators may inhibit hypoxic pulmonary vasoconstriction and impair gas exchange. The efficacy and safety of iloprost inhalation was assessed in 67 patients with PH associated with COPD (COPD-PH), diagnosed by right heart catheterization. Of these, 37 patients had severe PH (mean pulmonary arterial pressure [mPAP] >35 mmHg or mPAP 25-35 mmHg with low cardiac index [<2.0 L⋅min-1⋅m-2]). All patients received a single 20 µg dose of iloprost via a nebulizer (4.4 µg delivered at the mouthpiece). No serious adverse events were reported. Hemodynamic and gas exchange parameters (arterial blood gas and shunt fraction [Qs/Qt]) were measured or calculated at baseline and 10 min after iloprost inhalation. mPAP decreased by 2.1 mmHg (95% CI, -3.3 to -1.0), pulmonary vascular resistance (PVR) decreased by 62.4 dyn⋅s⋅cm-5 (95% CI, -92.9 to -31.8), and cardiac output increased by 0.4 L⋅min-1 (95% CI, 0.2-0.5). There was a more significant decline in PVR in patients with severe COPD-PH than in those with nonsevere COPD-PH. Hypoxemia and intrapulmonary shunt were more extreme in patients with severe COPD-PH. However, there were no significant differences in arterial blood gas and Qs/Qt between patients with nonsevere and severe forms of COPD-PH. In conclusion, iloprost improved pulmonary hemodynamics without detrimental effects on arterial oxygenation in patients with COPD-PH, even in those with severe PH. These findings suggest that the short-term use of iloprost in patients with COPD-PH is effective and well tolerated.

Development of a diagnosis model for coronary artery disease.

BACKGROUND: The purpose of this study was to develop a coronary artery disease (CAD) prediction model that optimally estimates the pre-test probability of CAD for patients suspected of CAD. METHODS AND RESULTS: This retrospective, multi-centre study included 7360 consecutive patients (4678 men, 57.87±11.42 years old; 2682 women, 61.60±9.58 years old) who underwent coronary angiography for evaluation of CAD. A prediction model was fitted for diagnosis of CAD with the help of eight significant risk factors including sex, age, smoking status, diabetes, hypertension, dyslipidaemia, serum creatinine and angina. All potential predictors were significantly associated with the presence of CAD. The prevalence of CAD was significantly higher in men than in women. The clinical model gives a relatively accurate prediction of CAD with an area under the curve (AUC) of 0.74 (95% CI, 0.88-0.96; P<0.001). Addition of angina to the prediction model improves the predictive precision of the model. The optimal cut-off for predicting CAD in this model was 0.79 with a sensitivity of 0.658 and a specificity of 0.709. CONCLUSION: A prediction model including age, sex, and cardiovascular risk factors allow for an accurate estimation of the pre-test probability of coronary artery disease in Chinese populations. This algorithm may be useful in making decisions relating to the diagnosis of CAD.

Short­term vagus nerve stimulation reduces myocardial apoptosis by downregulating microRNA­205 in rats with chronic heart failure.

Previous studies have reported that short­term vagus nerve stimulation (VNS) improves cardiac function in rats with chronic heart failure (CHF). The molecular mechanisms are unclear. The potential effect of microRNA (miR)­205 in apoptosis of short­term VNS was examined. A total of 3 weeks after inducing CHF, the rats were divided into three groups: Sham stimulation in sham operated rats, sham stimulation in CHF rats (CHF­SS), and treated with VNS in CHF rats (CHF­VNS). The right vagus nerve of the neck was stimulated for 72 h in CHF rats with rectangular pulses of 40 msec duration at 1 Hz and 5 V. miR­205 was focused on, which exhibited differential expression in the miRNA microarray analysis of CHF rats, and the effects of VNS on apoptosis were examined. It was verified that the expression level of miR­205 in the CHF­SS group was increased, and the expression was reduced in the CHF­VNS group. Furthermore, mimics or inhibitor of miR­205 was transfected into H9c2 to investigate its function on apoptosis. Baculoviral IAP repeat­containing protein 2 (Birc2) was confirmed a target of miR­205 through a dual luciferase reporter assay and western blotting. It was demonstrated that downregulated miR­205 decreased apoptosis in H9c2 cells. The apoptosis­associated proteins were further detected in H9c2 cells and rat tissue. The mRNA and protein expression levels of caspase­3 and Bcl­2­associated X protein were decreased in the CHF­VNS group, the expression of Birc2 and B­cell lymphoma 2 were increased. The results were consistent with the in vitro study in the miR­205 inhibitor group. The present study demonstrated that short­term VNS decreased apoptosis by downregulating miR­205 in rats with CHF. Therefore, the results of the present study provide basic evidence for short­term VNS in the clinical treatment of CHF.

Genetic Effects on Sensorineural Hearing Loss and Evidence-based Treatment for Sensorineural Hearing Loss.

In this article, the mechanism of inheritance behind inherited hearing loss and genetic susceptibility in noise-induced hearing loss are reviewed. Conventional treatments for sensorineural hearing loss (SNHL), i.e. hearing aid and cochlear implant, are effective for some cases, but not without limitations. For example, they provide little benefit for patients of profound SNHL or neural hearing loss, especially when the hearing loss is in poor dynamic range and with low frequency resolution. We emphasize the most recent evidence-based treatment in this field, which includes gene therapy and allotransplantation of stem cells. Their promising results have shown that they might be options of treatment for profound SNHL and neural hearing loss. Although some treatments are still at the experimental stage, it is helpful to be aware of the novel therapies and endeavour to explore the feasibility of their clinical application.

Detection of circulating IgG antibodies to apolipoprotein B100 in acute myocardial infarction.

A number of studies have reported an association between increased levels of antibodies against oxidized low-density lipoprotein (oxLDL) and cardiovascular disease, but the anti-oxLDL antibody has not been confirmed to serve as an effective biomarker for prediction of acute myocardial infarction (AMI). Apolipoprotein B100 (ApoB100)-derived peptide fragments generated by proteolytic degradation and aldehyde modification are the major antigens in oxLDL, and so the present work was undertaken to detect circulating IgG for Apo-B100-derived peptide antigens. An in-house enzyme-linked immunosorbent assay (ELISA) was developed with eight ApoB100-derived peptide antigens (Ag1-Ag8) to detect circulating anti-ApoB100 IgG levels in 267 patients with AMI and 201 control subjects. Binary logistic regression analysis revealed that circulating IgG for Ag1 was significantly higher in the patient group than the control group (P < 0.001) after adjustment for age, gender, smoking, hypertension, diabetes and circulating levels of cholesterol, HDL, LDL, ApoA and ApoB100. None of the other seven antigens detected an increase in IgG levels in AMI patients compared with control subjects. Spearman correlation analysis showed no correlation between IgG antibody for Ag1 and clinical characteristics. In conclusion, the linear peptide antigens derived from ApoB100 may be suitable for the development of an ELISA antibody test for prediction of AMI, although further confirmation is still needed in large-scale clinical studies.

Sphingosine-1-phosphate receptor agonist, FTY720, restores coronary flow reserve in diabetic rats.

BACKGROUND: Impairment of coronary flow reserve (CFR) has been generally demonstrated in diabetic patients and animals with microvascular complications but without obvious obstructive coronary atherosclerosis. There have been few studies investigating CFR in cases of relatively well-controlled therapy. The purpose of this study is to evaluate the effect of treatment with a Sphingosine-1-phosphate (S1P) receptor potent agonist, FTY720, on early diabetic rats in terms of CFR. METHODS AND RESULTS: Male Sprague-Dawley (SD) rats were divided into 3 groups: (1) streptozotocin-uninjected rats (control rats); (2) streptozotocin-injected hyperglycemic rats (diabetic group); and (3) FTY720-fed and streptozotocin-injected hyperglycemic rats. FTY720 (1.25 mg/kg per day orally) was administrated for 9 weeks in SD rats (from 6 weeks old to 15 weeks old). CFR was evaluated by (13)NH3-positron emission tomography. No obvious pathological changes of macrovascular atherosclerosis were observed in each group. Diabetic rats had impaired CFR compared with the control group (1.39±0.26 vs. 1.94±0.24, P<0.05). Treatment with FTY720 for 9 weeks attenuated the heart histological changes and improved CFR in 32% of diabetic rats (1.84±0.36 vs. 1.39±0.26, P<0.05). CONCLUSIONS: In summary, long-term therapy with the Sphingosine-1-phosphate receptor agonist, FTY720, improved CFR by attenuating the heart histological changes, and it might have a beneficial effect on coronary microvascular function in diabetic rats.

Common polymorphisms in the interleukin-6 gene and myocardial infarction risk: a meta-analysis.

BACKGROUND: Interleukin-6 (IL-6) plays a critical role in the development and progression of cardiovascular disease. Emerging evidence suggests that two common polymorphisms (-174 G/C and -572 G/C) in the IL-6 gene might have an impact on an individual's susceptibility to myocardial infarction (MI), but individually published results are inconclusive. This meta-analysis aimed to derive a more precise estimation of the relationship between IL-6 -174 G/C and -572 G/C polymorphisms and MI risk. METHOD: An extensive literary search for relevant studies was conducted in PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine (CBM), and China National Knowledge Infrastructure (CNKI) databases from their inception through August 1st, 2013. A meta-analysis was then performed using the STATA 12.0 software. The crude odds ratios (OR) with 95% confidence intervals (CI) were calculated. RESULTS: Eleven case-control studies were included with a total of 10,252 subjects, including 5429 MI patients and 4823 healthy controls. Our meta-analysis results indicated that IL-6 -174 G/C polymorphism may increase the risk of MI (C allele vs. G allele: OR=1.07, 95% CI: 1.01-1.14, p=0.018; GC+CC vs. GG: OR=1.14, 95% CI: 1.04-1.24, p=0.003; respectively). However, our results showed no significant association between IL-6 -572 G/C polymorphism and MI risk (C allele vs. G allele: OR=0.88, 95% CI: 0.75-1.03, p=0.098; GC+CC vs. GG: OR=0.87, 95% CI: 0.70-1.07, p=0.173; respectively). No publication bias was detected in this meta-analysis. CONCLUSION: The current meta-analysis suggests that IL-6 -174 G/C polymorphism may contribute to MI susceptibility. Thus, detection of IL-6 -174 G/C polymorphisms may be a promising biomarker for the early detection of MI. However, IL-6 -572 G/C polymorphism may not associate with the risk of MI.

Glutathione S-transferase M1 polymorphism and coronary heart disease susceptibility: a meta-analysis involving 47,596 subjects.

BACKGROUND: Many studies have investigated the association between glutathione S-transferase M1 (GSTM1) null genotype and the risk of coronary heart disease (CHD). However, the effect of the GSTM1 null genotype on CHD is still unclear because of apparent inconsistencies among those studies. A meta-analysis was performed to characterise the relationship more accurately. METHODS: Pubmed, Embase, and Web of Science were searched. We estimated the summary odds ratio (OR) with a 95% confidence interval (95% CI) to assess the association. RESULTS: Up to 26 case-control studies with 13,929 CHD cases and 33,667 control cases were included into this meta-analysis. Meta-analysis of the 26 studies showed that GSTM1 null genotype was associated with the risk of CHD (random effects OR=1.35, 95% CI 1.00 to 1.83). After adjustment for heterogeneity, meta-analysis showed that GSTM1 null genotype was not associated with increased risk of CHD in the total population (fixed effects OR=1.01, 95% CI 0.95 to 1.07). In the subgroup analysis by ethnicity, increased risks were not found for either Caucasians (OR=1.36, 95% CI=0.96-1.92) or Asians (OR=1.28, 95% CI=0.91-1.80). When stratified by smoking status, in the subgroup of smokers, GSTM1 null genotype was significantly associated with increased CHD risk (random effects OR=1.64, 95% CI 1.02 to 2.64). No evidence of publication bias was observed. CONCLUSION: In conclusion, this meta-analysis suggested that there is overall lack of association between GSTM1 genotypes and CHD risk, however, GSTM1 null genotype when combining with smoking history may contribute to CHD susceptibility.